I've killed three smaller ones with the 6.5x55mm; my Dad killed a big bull with a heart shot from a .22-250, but we sure don't recommend it and have learned a lot since those early buffalo hunts; I've killed one with the .30/30 and the .300H&H, and don't recommend those either (although using the Hydro projectile would be an improvement out of the latter); mostly I use and recommend the big bores - .450/400 3" NE, .416 Rigby, .458WM and .500NE. Many locals use smaller calibres and swear by them, but they are more shooters than hunters, and don't tell about the ones that got away wounded.